Abstract
Non-specific X-linked mental retardation (MRX) is a very common disorder which affects ~1 in 600 males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity which is evident from linkage studies. Recently, a collaborative study using the candidate gene approach demonstrated the presence of mutations in GDIα, a Rab GDP-dissociation inhibitor encoded by a gene localized in Xq28, associated with non-specific mental retardation. GDIα is mainly a brain-specific protein that plays a critical role in the recycling of Rab GTPases involved in membrane vesicular transport. The study presented here was designed to assess the prevalence of mutations in the GDIα in mentally retarded patients and to discuss the clinical phenotypes observed in affected individuals. Mutation screening of the whole coding region of the GDIα gene, using a combination of denaturing gradient gel electrophoresis and direct sequencing, was carried out in 164 patients found negative for expansions across the FRAXA GCC repeat. In addition to the nonsense mutation recently reported in MRX48, we have identified a novel missense mutation in exon 11 of the GDIα gene in one familial form of non-specific mental retardation. In this family (family R), all affected males show moderate to severe mental retardation, and the X-linked semidominant inheritance is strongly suggested by the severe phenotypes in males with respect to mildly affected females or unaffected obligatory carriers. This study showed that the prevalence of GDIα mutations in non-specific mental retardation could be estimated to be 0.5-1%, and molecular diagnosis and genetic counselling in some cases of nonspecific mental handicap can now be provided.
| Original language | English |
|---|---|
| Pages (from-to) | 1311-1315 |
| Number of pages | 5 |
| Journal | Human Molecular Genetics |
| Volume | 7 |
| Issue number | 8 |
| Publication status | Published - Aug 1998 |
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ASJC Scopus subject areas
- Genetics
Cite this
Non-specific X-linked semidominant mental retardation by mutations in a Rab GDP-dissociation inhibitor. / Bienvenu, Thierry; Des Portes, Vincent; Saint Martin, Anne; McDonell, Nathalie; Billuart, Pierre; Carrié, Alain; Vinet, Marie Claude; Couvert, Philippe; Toniolo, Daniela; Ropers, Hans Hilger; Moraine, Claude; Van Bokhoven, Hans; Fryns, Jean Pierre; Kahn, Axel; Beldjord, Cherif; Chelly, Jamel.
In: Human Molecular Genetics, Vol. 7, No. 8, 08.1998, p. 1311-1315.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Non-specific X-linked semidominant mental retardation by mutations in a Rab GDP-dissociation inhibitor
AU - Bienvenu, Thierry
AU - Des Portes, Vincent
AU - Saint Martin, Anne
AU - McDonell, Nathalie
AU - Billuart, Pierre
AU - Carrié, Alain
AU - Vinet, Marie Claude
AU - Couvert, Philippe
AU - Toniolo, Daniela
AU - Ropers, Hans Hilger
AU - Moraine, Claude
AU - Van Bokhoven, Hans
AU - Fryns, Jean Pierre
AU - Kahn, Axel
AU - Beldjord, Cherif
AU - Chelly, Jamel
PY - 1998/8
Y1 - 1998/8
N2 - Non-specific X-linked mental retardation (MRX) is a very common disorder which affects ~1 in 600 males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity which is evident from linkage studies. Recently, a collaborative study using the candidate gene approach demonstrated the presence of mutations in GDIα, a Rab GDP-dissociation inhibitor encoded by a gene localized in Xq28, associated with non-specific mental retardation. GDIα is mainly a brain-specific protein that plays a critical role in the recycling of Rab GTPases involved in membrane vesicular transport. The study presented here was designed to assess the prevalence of mutations in the GDIα in mentally retarded patients and to discuss the clinical phenotypes observed in affected individuals. Mutation screening of the whole coding region of the GDIα gene, using a combination of denaturing gradient gel electrophoresis and direct sequencing, was carried out in 164 patients found negative for expansions across the FRAXA GCC repeat. In addition to the nonsense mutation recently reported in MRX48, we have identified a novel missense mutation in exon 11 of the GDIα gene in one familial form of non-specific mental retardation. In this family (family R), all affected males show moderate to severe mental retardation, and the X-linked semidominant inheritance is strongly suggested by the severe phenotypes in males with respect to mildly affected females or unaffected obligatory carriers. This study showed that the prevalence of GDIα mutations in non-specific mental retardation could be estimated to be 0.5-1%, and molecular diagnosis and genetic counselling in some cases of nonspecific mental handicap can now be provided.
AB - Non-specific X-linked mental retardation (MRX) is a very common disorder which affects ~1 in 600 males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity which is evident from linkage studies. Recently, a collaborative study using the candidate gene approach demonstrated the presence of mutations in GDIα, a Rab GDP-dissociation inhibitor encoded by a gene localized in Xq28, associated with non-specific mental retardation. GDIα is mainly a brain-specific protein that plays a critical role in the recycling of Rab GTPases involved in membrane vesicular transport. The study presented here was designed to assess the prevalence of mutations in the GDIα in mentally retarded patients and to discuss the clinical phenotypes observed in affected individuals. Mutation screening of the whole coding region of the GDIα gene, using a combination of denaturing gradient gel electrophoresis and direct sequencing, was carried out in 164 patients found negative for expansions across the FRAXA GCC repeat. In addition to the nonsense mutation recently reported in MRX48, we have identified a novel missense mutation in exon 11 of the GDIα gene in one familial form of non-specific mental retardation. In this family (family R), all affected males show moderate to severe mental retardation, and the X-linked semidominant inheritance is strongly suggested by the severe phenotypes in males with respect to mildly affected females or unaffected obligatory carriers. This study showed that the prevalence of GDIα mutations in non-specific mental retardation could be estimated to be 0.5-1%, and molecular diagnosis and genetic counselling in some cases of nonspecific mental handicap can now be provided.
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UR - http://www.scopus.com/inward/citedby.url?scp=7344219887&partnerID=8YFLogxK
M3 - Article
C2 - 9668174
AN - SCOPUS:7344219887
VL - 7
SP - 1311
EP - 1315
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 8
ER -